IL1{beta}/IL1R Signaling Promotes Mesothelioma Development
Exposure to asbestos is causally associated with the development of malignant mesothelioma, a cancer of cells lining the internal body cavities. Malignant mesothelioma is an aggressive cancer resistant to all current therapies. Once inhaled or ingested, asbestos causes inflammation in and around tissues that come in contact with these carcinogenic fibers. Recent studies suggest that inflammation is a major contributing factor in the development of many types of cancer, including malignant mesothelioma. The NALP3/NLRP3 inflammasome, including the component ASC, is thought to be an important mediator of inflammation in cells...
Source: Cancer Prevention Research - April 30, 2016 Category: Cancer & Oncology Authors: Kadariya, Y., Menges, C. W., Talarchek, J., Cai, K. Q., Klein-Szanto, A. J., Pietrofesa, R. A., Christofidou-Solomidou, M., Cheung, M., Mossman, B. T., Shukla, A., Testa, J. R. Tags: Research Articles Source Type: research
Clinical Trial of 2-Phenethyl Isothiocyanate
2-Phenethyl isothiocyanate (PEITC), a natural product found as a conjugate in watercress and other cruciferous vegetables, is an inhibitor of the metabolic activation and lung carcinogenicity of the tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in F344 rats and A/J mice. We carried out a clinical trial to determine whether PEITC also inhibits the metabolic activation of NNK in smokers. Cigarette smokers were recruited and asked to smoke cigarettes containing deuterium-labeled [pyridine-D4]NNK for an acclimation period of at least 1 week. Then subjects were randomly assigned to one of two arms: PEI...
Source: Cancer Prevention Research - April 30, 2016 Category: Cancer & Oncology Authors: Yuan, J.-M., Stepanov, I., Murphy, S. E., Wang, R., Allen, S., Jensen, J., Strayer, L., Adams-Haduch, J., Upadhyaya, P., Le, C., Kurzer, M. S., Nelson, H. H., Yu, M. C., Hatsukami, D., Hecht, S. S. Tags: Research Articles Source Type: research
Soy Effects on Estrogen Pathways in the Pubertal Breast
Endogenous estrogens influence mammary gland development during puberty and breast cancer risk during adulthood. Early-life exposure to dietary or environmental estrogens may alter estrogen-mediated processes. Soy foods contain phytoestrogenic isoflavones (IF), which have mixed estrogen agonist/antagonist properties. Here, we evaluated mammary gland responses over time in pubertal female cynomolgus macaques fed diets containing either casein/lactalbumin (n = 12) or soy protein containing a human-equivalent dose of 120 mg IF/day (n = 17) for approximately 4.5 years spanning menarche. We assessed estrogen receptor (ER) expre...
Source: Cancer Prevention Research - April 30, 2016 Category: Cancer & Oncology Authors: Dewi, F. N., Wood, C. E., Willson, C. J., Register, T. C., Lees, C. J., Howard, T. D., Huang, Z., Murphy, S. K., Tooze, J. A., Chou, J. W., Miller, L. D., Cline, J. M. Tags: Research Articles Source Type: research
Statins for Breast Cancer Prevention
Statins have the potential to reduce breast cancer incidence and recurrence as shown in both epidemiologic and laboratory studies. The purpose of this study was to evaluate the effect of a lipophilic statin, atorvastatin, on breast cancer biomarkers of risk [mammographic density (MD) and insulin growth factor 1 (IGF-1)] in high-risk premenopausal women.
Premenopausal women at increased risk for breast cancer received either 40 mg of atorvastatin or placebo for 1 year. Biomarker assessment was performed prior to initiation and at completion of study medication. MD was determined using both Breast Imaging Reporting and Data ...
Source: Cancer Prevention Research - April 30, 2016 Category: Cancer & Oncology Authors: Ji, Y., Rounds, T., Crocker, A., Sussman, B., Hovey, R. C., Kingsley, F., Muss, H. B., Garber, J. E., Wood, M. E. Tags: Research Articles Source Type: research
Mammary Fat-Derived Lysophospholipids Promote Cancer
Lysophosphatidic acid (LPA), acting in an autocrine or paracrine fashion through G protein–coupled receptors, has been implicated in many physiologic and pathologic processes, including cancer. LPA is converted from lysophosphatidylcholine (LPC) by the secreted phospholipase autotaxin (ATX). Although various cell types can produce ATX, adipocyte-derived ATX is believed to be the major source of circulating ATX and also to be the major regulator of plasma LPA levels. In addition to ATX, adipocytes secrete numerous other factors (adipokines); although several adipokines have been implicated in breast cancer biology, th...
Source: Cancer Prevention Research - April 30, 2016 Category: Cancer & Oncology Authors: Volden, P. A., Skor, M. N., Johnson, M. B., Singh, P., Patel, F. N., McClintock, M. K., Brady, M. J., Conzen, S. D. Tags: Research Articles Source Type: research
Microbiome and CIN Risk
It is increasingly recognized that microbes that reside in and on human body sites play major roles in modifying the pathogenesis of several diseases, including cancer. However, specific microbes or microbial communities that can be mechanistically linked to cervical carcinogenesis remain largely unexplored. The purpose of the study was to examine the association between cervical microbiota and high-grade cervical intraepithelial neoplasia (CIN 2+) in women infected with high-risk (HR) human papillomaviruses (HPV) and to assess whether the cervical microbiota are associated with oxidative DNA damage as indicated by the pre...
Source: Cancer Prevention Research - April 30, 2016 Category: Cancer & Oncology Authors: Piyathilake, C. J., Ollberding, N. J., Kumar, R., Macaluso, M., Alvarez, R. D., Morrow, C. D. Tags: Research Articles Source Type: research
Ki-67: Biomarkers in Presurgical Breast Cancer Trial
In breast cancer presurgical trials, the Ki-67 labeling index predicts disease outcome and offers clues to the preventive potential of drugs. We conducted a placebo-controlled trial to evaluate the activity of exemestane and celecoxib before surgery. The main endpoint was the change in Ki-67. Secondary endpoints were the modulation of circulating biomarkers. Postmenopausal women with histologically confirmed estrogen receptor–positive breast cancer were randomly assigned to exemestane 25 mg/day (n = 50), or celecoxib 800 mg/day (n = 50), or placebo (n = 25) for 6 weeks before surgery. Changes in biomarkers were analy...
Source: Cancer Prevention Research - April 30, 2016 Category: Cancer & Oncology Authors: Aristarco, V., Serrano, D., Gandini, S., Johansson, H., Macis, D., Guerrieri-Gonzaga, A., Lazzeroni, M., Feroce, I., Pruneri, G., Pagani, G., Toesca, A., Caldarella, P., DeCensi, A., Bonanni, B. Tags: Research Articles Source Type: research
Mammary Tumor Growth in Formerly Obese Mice
Using a murine model of basal-like breast cancer, we tested the hypothesis that chronic obesity, an established breast cancer risk and progression factor in women, induces mammary gland epigenetic reprogramming and increases mammary tumor growth. Moreover, we assessed whether the obesity-induced epigenetic and protumor effects are reversed by weight normalization. Ovariectomized female C57BL/6 mice were fed a control diet or diet-induced obesity (DIO) regimen for 17 weeks, resulting in a normal weight or obese phenotype, respectively. Mice on the DIO regimen were then randomized to continue the DIO diet or were switched to...
Source: Cancer Prevention Research - April 30, 2016 Category: Cancer & Oncology Authors: Rossi, E. L., de Angel, R. E., Bowers, L. W., Khatib, S. A., Smith, L. A., Van Buren, E., Bhardwaj, P., Giri, D., Estecio, M. R., Troester, M. A., Hair, B. Y., Kirk, E. L., Gong, T., Shen, J., Dannenberg, A. J., Hursting, S. D. Tags: Research Articles Source Type: research
Limitations of Driver/Passenger Model
Mutations detected in cancers are often divided into "drivers" and "passengers." We suggest that this classification is potentially misleading for purposes of early detection and prevention. Specifically, some mutations are frequent in tumors and thus appear to be drivers, but are poor predictors of cancer; other mutations are individually rare and thus appear to be passengers, but may collectively explain a large proportion of risk. The assumptions bundled into the terms "driver" and "passenger" can lead to misunderstandings of neoplastic progression, with unintended consequences including overdiagnosis, overtreatment, an...
Source: Cancer Prevention Research - April 30, 2016 Category: Cancer & Oncology Authors: Kuhner, M. K., Kostadinov, R., Reid, B. J. Tags: Commentary Source Type: research
AAI-Induced Hepatic Premalignant Alterations
Aristolochic acid I (AAI) existing in plant drugs from Aristolochia species is an environmental human carcinogen associated with urothelial cancer. Although gene association network analysis demonstrated gene expression profile changes in the liver of human TP53 knock-in mice after acute AAI exposure, to date, whether AAI causes hepatic tumorigenesis is still not confirmed. Here, we show that hepatic premalignant alterations appeared in canines after a 10-day AAI oral administration (3 mg/kg/day). We observed c-Myc oncoprotein and oncofetal RNA-binding protein Lin28B overexpressions accompanied by cancer progenitor-like ce...
Source: Cancer Prevention Research - March 30, 2016 Category: Cancer & Oncology Authors: Jin, K., Su, K.-k., Li, T., Zhu, X.-q., Wang, Q., Ge, R.-s., Pan, Z.-f., Wu, B.-w., Ge, L.-j., Zhang, Y.-h., Wang, Y.-f., Shen, G.-f., Zhu, D.-y., Xiang, C.-s., Li, L.-j., Lou, Y.-j. Tags: Research Articles Source Type: research
Serum Glycan Markers for NSCLC
Previous studies have suggested occurrence of altered serum glycan profiles in patients with lung cancer. Here, we aimed to determine the predictive value of serum glycans to distinguish non–small cell lung cancer (NSCLC) cases from controls in prediagnostic samples using a previously validated predictive protein marker pro-SFTPB, as anchor. Blinded prediagnostic serum samples were obtained from the Carotene and Retinol Efficacy Trial (CARET), and included a discovery set of 100 NSCLC cases and 199 healthy controls. A second test set consisted of 108 cases and 216 controls. Cases and controls were matched for age at ...
Source: Cancer Prevention Research - March 30, 2016 Category: Cancer & Oncology Authors: Ruhaak, L. R., Stroble, C., Dai, J., Barnett, M., Taguchi, A., Goodman, G. E., Miyamoto, S., Gandara, D., Feng, Z., Lebrilla, C. B., Hanash, S. Tags: Research Articles Source Type: research
Bisphosphonate Activates Human Breast T Cells
Developing strategies to enhance cancer prevention is a paramount goal, particularly given recent concerns about surgical treatment of preinvasive states such as ductal carcinoma in situ. Promoting effective immunosurveillance by leukocytes that scan for nascent neoplastic transformations represents a potential means to achieve this goal. Because most breast cancers arise within the ductal epithelium, enhancing protective immunosurveillance will likely necessitate targeting one or more of the distinctive lymphocyte types found in these sites under normal conditions. Here, we have characterized the intraepithelial lymphocyt...
Source: Cancer Prevention Research - March 30, 2016 Category: Cancer & Oncology Authors: Zumwalde, N. A., Haag, J. D., Sharma, D., Mirrielees, J. A., Wilke, L. G., Gould, M. N., Gumperz, J. E. Tags: Research Articles Source Type: research
C3 Complex and AZD4547 on UVB-Induced Epidermal Hyperplasia
Aggressive cutaneous squamous cell carcinoma (cSCC) of the skin is the second most common type of skin cancer in the United States due to high exposure to ultraviolet B (UVB) radiation. In our previous studies, Curcumin C3 complex (C3), a standardized preparation of three curcumonoids, delayed UVB-induced tumor incidence and inhibited multiplicity. Exposure to UVB activates mTOR and FGFR signaling that play a key role in skin tumorigenesis. The purpose of this study was to investigate the efficacy of C3 complex to afford protection against acute UVB-induced hyperproliferation by targeting the mTOR and FGFR signaling pathwa...
Source: Cancer Prevention Research - March 30, 2016 Category: Cancer & Oncology Authors: Khandelwal, A. R., Rong, X., Moore-Medlin, T., Ekshyyan, O., Abreo, F., Gu, X., Nathan, C.-A. O. Tags: Research Articles Source Type: research
Biomarker Evaluation for Premalignant Disease In Silico
This study demonstrates how the use of a mechanistic framework provided by computational modeling can diminish empirical constraints on biomarker development. Cancer Prev Res; 9(4); 283–95. ©2016 AACR. (Source: Cancer Prevention Research)
Source: Cancer Prevention Research - March 30, 2016 Category: Cancer & Oncology Authors: Dhawan, A., Graham, T. A., Fletcher, A. G. Tags: Research Articles Source Type: research
Omega-3 Fatty Acids, BMI, and Breast Density
Preclinical data indicate that omega-3 fatty acids (n-3FA) potentiate the chemopreventive effect of the antiestrogen (AE) tamoxifen against mammary carcinogenesis. The role of n-3FA in breast cancer prevention in humans is controversial. Preclinical and epidemiologic data suggest that n-3FA may be preferentially protective in obese subjects. To directly test the protective effect of n-3FA against breast cancer, we conducted a 2-year, open-label randomized clinical trial in 266 healthy postmenopausal women (50% normal weight, 30% overweight, 20% obese) with high breast density (BD; ≥25%) detected on their routine screeni...
Source: Cancer Prevention Research - March 30, 2016 Category: Cancer & Oncology Authors: Sandhu, N., Schetter, S. E., Liao, J., Hartman, T. J., Richie, J. P., McGinley, J., Thompson, H. J., Prokopczyk, B., DuBrock, C., Signori, C., Hamilton, C., Calcagnotto, A., Trushin, N., Aliaga, C., Demers, L. M., El-Bayoumy, K., Manni, A. Tags: Research Articles Source Type: research
